Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy.

Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the overproduction of white blood cells, leading to symptoms such as fatigue, infections, and other complications. CML patients must take measures to prevent infections to mitigate the exacerbation of cancer cell proliferation and comorbidities. Methods: This study investigated whether vitamin C can suppress the hyperinflammatory activation of K-562 cells induced by lipopolysaccharide (LPS) and whether purinergic signaling (ATP and P2X7 receptor) and autophagy play a role in it. Two different doses of vitamin C (5 µg/mL and 10 µg/mL) were employed, along with the lysosome inhibitor chloroquine (CQ; 100 µM), administered 2 h prior to LPS stimulation (10 ng/mL) for a duration of 22 h in K-562 cells (3 × 105 cells/mL/well). Results: Both doses of vitamin C reduced the release of interleukin-6 (IL-6) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) and tumor necrosis factor (TNF) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) induced by LPS. Furthermore, in LPS + CQ-stimulated cells, vitamin C at a concentration of 10 µg/mL inhibited the expression of LC3-II (p < 0.05). Conversely, both doses of vitamin C led to the release of the anti-inflammatory cytokine interleukin-10 (IL-10) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01), while only the 10 µg/mL dose of vitamin C induced the release of Klotho (10 µg/mL, p < 0.01). In addition, both doses of vitamin C reduced the accumulation of ATP (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) and decreased the expression of the P2X7 receptor at the mRNA level. Conclusions: Vitamin C inhibits the hyperinflammatory state induced by LPS in K-562 cells, primarily by inhibiting the ATP accumulation, P2X7 receptor expression, and autophagy signaling.

Effects of a Cycling versus Running HIIT Program on Fat Mass Loss and Gut Microbiota Composition in Men with Overweight/Obesity.

PURPOSE: High-intensity interval training (HIIT) can efficiently decrease total and (intra-)abdominal fat mass (FM); however, the effects of running versus cycling HIIT programs on FM reduction have not been compared yet. In addition, the link between HIIT-induced FM reduction and gut microbiota must be better investigated. The aim of this study was to compare the effects of two 12-wk HIIT isoenergetic programs (cycling vs running) on body composition and fecal microbiota composition in nondieting men with overweight or obesity. METHODS: Sixteen men (age, 54.2 ± 9.6 yr; body mass index, 29.9 ± 2.3 kg·m -2 ) were randomly assigned to the HIIT-BIKE (10 × 45 s at 80%-85% of maximal heart rate, 90-s active recovery) or HIIT-RUN (9 × 45 s at 80%-85% of maximal heart rate, 90-s active recovery) group (3 times per week). Dual-energy x-ray absorptiometry was used to determine body composition. Preintervention and postintervention fecal microbiota composition was analyzed by 16S rRNA gene sequencing, and diet was controlled. RESULTS: Overall, body weight, and abdominal and visceral FM decreased over time ( P < 0.05). No difference was observed for weight, total body FM, and visceral FM between groups (% change). Conversely, abdominal FM loss was greater in the HIIT-RUN group (-16.1% vs -8.3%; P = 0.050). The α-diversity of gut microbiota did not vary between baseline and intervention end and between groups, but was associated with abdominal FM change ( r = -0.6; P = 0.02). The baseline microbiota profile and composition changes were correlated with total and abdominal/visceral FM losses. CONCLUSIONS: Both cycling and running isoenergetic HIIT programs improved body composition in men with overweight/obesity. Baseline intestinal microbiota composition and its postintervention variations were correlated with FM reduction, strengthening the possible link between these parameters. The mechanisms underlying the greater abdominal FM loss in the HIIT-RUN group require additional investigations.

Six HIT Sessions Improve Cardiorespiratory Fitness and Metabolic Flexibility in Insulin Resistant and Insulin Sensitive Adolescents with Obesity.

To evaluate the effect of high-intensity interval training (HIT) on the cardiorespiratory performance and substrate oxidation pattern in insulin-resistant and insulin-sensitive obese adolescents. METHODS: We recruited 25 obese adolescents in three schools, and trained them in six HIT sessions, comprising of six series at 100% and recovery at 50% peak velocity (Vpeak). For the evaluation, the participants were divided into two groups: insulin-resistant (IR, n = 12; HOMA index ≥3.16) and insulin-sensitive (IS, n = 13). All participants underwent cardiopulmonary and indirect calorimetry testing. We compared the effects of HIT before and after the intervention among the two groups. The data were analyzed using Student's t and Mann-Whitney (intergroup comparisons) and Student's t and Wilcoxon (pre- and post-training comparisons) tests; and Cohen's d (influence of HIT). RESULTS: There was a significant post-training increase in Vpeak, oxygen consumption (VO2), velocity (V), and heart rate (HR) at the exertion intensity at the first ventilatory anaerobic threshold (VAT1) in both groups (p < 0.05; d < 0.02). The exercise promoted changes in substrate oxidation rates of the groups, with an increase in carbohydrate oxidation (CHOox) for both IR (p = 0.064) and IS (p = 0.034). CONCLUSION: Six HIT sessions improved cardiorespiratory performance in both groups and increased CHOox in insulin-sensitive obese adolescents, suggesting its utility for increasing physical fitness and controlling glycemia in these population groups.

Strategies to Prevent Sarcopenia in the Aging Process: Role of Protein Intake and Exercise.

Sarcopenia is one of the main issues associated with the process of aging. Characterized by muscle mass loss, it is triggered by several conditions, including sedentary habits and negative net protein balance. According to World Health Organization, it is expected a 38% increase in older individuals by 2025. Therefore, it is noteworthy to establish recommendations to prevent sarcopenia and several events and comorbidities associated with this health issue condition. In this review, we discuss the role of these factors, prevention strategies, and recommendations, with a focus on protein intake and exercise.

Caffeine and Exercise Performance: Possible Directions for Definitive Findings.

Caffeine is one of the most studied supplements in the world. Studies correlate its use to increased exercise performance in endurance activities, as well as its possible ergogenic effects for both intermittent and strength activities. Recent findings show that caffeine may increase or decrease exercise performance. These antagonist responses may occur even when using the same dosage and for individuals with the same characteristics, making it challenging to explain caffeine's impact and applicability. This review article provides an analytic look at studies involving the use of caffeine for human physical performance, and addresses factors that could influence the ergogenic effects of caffeine on different proposed activities. These factors subdivide into caffeine effects, daily habits, physiological factors, and genetic factors. Each variable has been focused on by discussions to research related to caffeine. A better understanding and control of these variables should be considered in future research into personalized nutritional strategies.

Crosstalk Between Skeletal Muscle and Immune System: Which Roles Do IL-6 and Glutamine Play?

The skeletal muscle was always seen from biomechanical and biochemical views. It is well-established that an active muscle brings many benefits for different body organs and tissues, including the immune system. Since the 1970s, many studies have shown the importance of regular exercise and physical activity in increasing the body's ability to fight opportunist infections, as well as a strategy to fight established diseases. This interaction was mainly attributed to the glutamine, a non-essential amino acid produced by the active skeletal muscle and primarily consumed by rapidly dividing cells, including lymphocytes and monocytes/macrophages, as their main source of energy. Therefore, these cells' function would be significantly improved by the presence of a bigger glutamine pool, facilitating phagocytosis, antigen-presentation, proliferative capacity, cytokine synthesis and release, among other functions. Despite its importance, glutamine is not the only molecule to connect these two tissues. The presence of cytokines is crucial for a proper immune system function. Many of them have well-established pro-inflammatory properties, while others are known for their anti-inflammatory role. Interleukin-6 (IL-6), however, has been in the center of many scientific discussions since it can act as pro- and anti-inflammatory cytokine depending on the tissue that releases it. Skeletal muscle is an essential source of IL-6 with anti-inflammatory properties, regulating the function of the immune cells after tissue injury and the healing process. Therefore, this review aims to discuss further the role of these four components (glutamine, and interleukin-6, and its interface with monocytes/macrophages, and lymphocytes) on the communication between the skeletal muscle and the immune system.

Probiotic supplementation in marathonists and its impact on lymphocyte population and function after a marathon: a randomized placebo-controlled double-blind study.

Probiotic supplementation arises as playing an immune-stimulatory role. High-intensity and -volume exercise can inhibit immune cell function, which threatens athletic performance and recovery. We hypothesized that 30 days of probiotic supplementation could stabilize the immune system of athletes preventing immune suppression after a marathon race. Twenty-seven male marathonists were double-blinded randomly into probiotic (Bifidobacterium-animalis-subsp.-Lactis (10 × 109) and Lactobacillus-Acidophilus (10 × 109) + 5 g of maltodextrin) and placebo (5 g of maltodextrin) group. They received 30 sachets and supplemented 1 portion/day during 30 days before the race. Blood were collected 30 days before (rest), 1 day before (pre), 1 h after (post) and 5 days after the race (recovery). Both chronic and acute exercise modulated a different T lymphocyte population (CD3+CD4-CD8- T-cells), increasing pre-race, decreasing post and returning to rest values at the recovery. The total number of CD8 T cell and the memory subsets statistically decreased only in the placebo group post-race. Pro-inflammatory cytokine production by stimulated lymphocytes decreased in the probiotic group after the supplementation period. 30 days of probiotic supplementation maintained CD8 T cell and effector memory cell population and played an immunomodulatory role in stimulated lymphocytes. Both, training and marathon modulated a non-classical lymphocyte population regardless of probiotic supplementation.

Effect of high intensity interval training on body composition in women before and after menopause: a meta-analysis.

NEW FINDINGS: What is the topic of this review? A meta-analysis of the efficacy of high intensity interval training (HIIT) in reducing weight, total fat mass (FM) and (intra)-abdominal FM in normal-weight and overweight/obese women before and after menopause. What advances does it highlight? HIIT programmes in women significantly decrease body weight and total and abdominal FM. Their effects are more evident in pre- than in postmenopausal women. Cycling HIIT seems more effective than running, especially in postmenopausal women, and training interventions longer than 8 weeks comprising three sessions a week should be promoted. ABSTRACT: High-intensity interval training (HIIT) is a stimulating modality for reducing body weight and adipose tissue. The purpose of this meta-analysis was to assess the efficacy of HIIT in reducing weight, total fat mass (FM) and (intra)-abdominal FM in normal-weight and overweight/obese women before and after menopause. A structured electronic search was performed to find all publications relevant to our review. Stratified analyses were made of hormonal status (pre- vs. postmenopausal state), weight, HIIT modalities (cycling vs. running), programme duration (< or ≥8 weeks) and the methods used to measure body composition (dual-energy X-ray absorptiometry vs. computed tomography, Magnetic Resonance Imaging and others). A total of 38 studies involving 959 subjects were included. Our meta-analysis showed that overall HIIT programmes significantly decrease weight, total and abdominal FM in women. Both normal weight and overweight/obese women lost total FM after HIIT protocols whereas HIIT was only effective in decreasing abdominal FM in women with excess adiposity. When pre- and postmenopausal women were considered separately, the effect of HIIT on weight, total and abdominal FM were only significant before menopause. Cycling HIIT seemed more effective than running, especially in postmenopausal women, and training interventions longer than 8 weeks comprising three sessions were more efficient. HIIT is a successful strategy to lose weight and FM in normal weight and overweight/obese women. However, further studies are still needed to draw meaningful conclusions about the real effectiveness of HIIT protocols in postmenopausal women.

Total genotype score and athletic status: An exploratory cross-sectional study of a Brazilian athlete cohort.

The purpose of the present study was to explore the ability of the total genotype score (TGS) for evaluation of the polygenic profile of elite athletes. Data from a Brazilian athlete cohort were used in this study, which included 368 athletes and 818 nonathletes. The TGS targeted to power athletes was computed using from two to 10 associated polymorphisms. In all models, the power group showed a higher TGS mean compared to the nonathlete group. In particular, scores using more associated polymorphisms showed stronger differences (P < 0.0001). Moreover, the more polymorphisms included in the score, the greater its discriminatory power. The frequency distribution of individuals according to the TGS computed using 10 associated polymorphisms showed that both the power group and the replication group were overrepresented in scores ≥60.0 (P < 0.0075). Individuals with a score ≥60.0 had an increased odds ratio (OR) of being an elite athlete compared to the nonathlete group (OR > 2.03; P < 0.006), although there were athletes with TGS values ranging from 15.0 to 90.0. By setting 60.0 as the cutoff point, the sensitivity and specificity of the TGS was approximately 30% and 82.5%, respectively. In conclusion, the TGS computed using 10 associated polymorphisms proved to be effective in discriminating the target athlete group, but with limited accuracy as evidenced by its sensitivity rate.

Creatine supplementation can improve impact control in high-intensity interval training.

OBJECTIVES: This study aimed to investigate the effects of creatine (Cr) supplementation on biomechanical parameters related to shock attenuation during a session of high-intensity interval training (HIIT). METHODS: A single-blinded, placebo-controlled, crossover design was adopted to test eight male elite soccer players during HIIT sessions under two conditions: after placebo supplementation and after Cr supplementation. HIIT test sessions consisted of an intermittent test (five bouts of running) with a constant load applied until exhaustion was reached. The vertical component of ground reaction force and electromyography data were recorded by Gaitway and Lynx-EMG Systems, respectively. Heart rate, rated perceived exertion (Borg's Scale) and lactate concentration information were also obtained. RESULTS: Cr supplementation did not affect heart rate, rated perceived exertion, and lactate concentration. Decreased values of magnitude of the first peak of the vertical component of ground reaction force (17.2-24.2%) and impulse of the first 50 ms (Imp50; 34.3%) were observed for Cr, but higher values of time to reach the first peak were detected for Cr compared with placebo. Significant modifications in muscle activation were also observed, mainly in the pre-activation phase, and changes were observed in intermediary bouts. CONCLUSIONS: Cr supplementation has the potential to influence biomechanical parameters related to impact control during a single session of HIIT based on running. In particular, the findings of the current study indicate possible improvements in shock attenuation and a safer practice of HIIT under Cr supplementation.

Probiotics and sports: A new magic bullet?

The use of probiotics in sports has been growing in the past years focusing on the attenuation of upper respiratory tract (URS) and gastrointestinal (GI) symptoms commonly present in endurance athletes. Researches shown different results and this may related to the probiotic strain, dose, period consumption or even the form of administration (capsules, sachets or fermented milk). These four factors directly influence in the probiotic's outcome and this question still remains unclear. Thus, the goal of this review is to clarify how these factors may influence the outcomes, approaching the major differences among studies, mechanisms by which the probiotic may contribute in sports field and applied conclusions. It was used 'probiotics', 'athletes', 'sports', 'exercise', 'athletes performance', 'immune response', 'intestinal symptoms' as keywords and its combinations and 20 original articles were selected for our purpose. All the articles were performed in healthy physically active people and/or athletes. Putting together, it was observed that athletes may benefit from probiotics consumption. It seems that multi strain ingested via sachet or fermented food and a larger period of consumption may shown better results at minimizing URS and GI symptoms. Also, specific species appears to have a role in exercise recovery. Therefore, the beneficial effect of probiotics in sports field is strictly dependent on the four factors abovementioned. The molecular mechanisms behind the probiotics effectiveness have not yet been elucidated and perhaps the biological assessments performed in the studies as well the few number of studies published did not answer the question yet.

Vitamin D, muscle recovery, sarcopenia, cachexia, and muscle atrophy.

The relevance of vitamin D to skeletal muscle metabolism has been highlighted in recent years. The interest arises from the important findings of studies demonstrating multiple effects of vitamin D on this tissue, which can be divided into genomic (direct effects) and non-genomic effects (indirect effects). Another important aspect to be considered in the study of vitamin D and muscle fiber metabolism is related to different expression of vitamin D receptor (VDR), which varies in muscle tissue depending on age, sex, and pathology. The correlation between low circulating levels of vitamin D and muscle metabolism disorders is documented in various contexts, including muscle recovery, atrophy, sarcopenia, and cachexia. The aim of this review was to analyze recent results of both in vitro and in vivo studies to address the relationship between vitamin D and skeletal muscle biology. The words muscle atrophy, muscle hypertrophy, sarcopenia, and cachexia were crossed over with vitamin D in a Pubmed search. All original contributions, along with reviews on the topic, were included, and no publications in the past 10 y were discarded. The papers retrieved different topics such as vitamin D in skeletal muscle; vitamin D in circulation; vitamin D, sarcopenia, and muscle atrophy; vitamin D and cachexia; and vitamin D and muscle recovery.

A new clinical perspective: Treating obesity with nutritional coaching versus energy-restricted diets.

Although current guidelines for obesity treatment endorse lifestyle modifications to achieve weight loss, energy-restricted diets are still the most commonly used method for the management of overweight. Diet restriction, however, not only is ineffective in promoting long-term weight loss but also may have more costs than benefits, predisposing the individual to fat regain. Several physiological and psychological mechanisms protect the body against starvation and explain how food restriction can promote paradoxically the opposite of what it is planned to achieve, triggering changes in energy metabolism, endocrine function and, thus, body composition. New approaches that focus on behavioral treatment without diet restriction, such as nutritional coaching, are showing strong growth that arises as an innovative way to create sustainable and effective lifestyle changes.

Improving Nutritional Habits With No Diet Prescription: Details of a Nutritional Coaching Process.

Thousands of dollars are spent today with policies encouraging physical activity and healthy eating, but nutritional consultation per se has continuously failed to yield consistent and lasting results. The aim of this case report is to detail and evaluate nutritional coaching (employing health coaching techniques) in promoting lifestyle changes, enabling improvement of nutritional and body composition associated parameters. The patient in this study had previously engaged in a series of different diet regimens, all of which failed in achieving the proposed aim. After 12 nutritional coaching sessions (one per week) with the strategy presented herein, reductions in body fat mass and in total body weight were attained. Nutritional habits also improved, as the patient showed decreased total energy intake, decreased fat intake, and increased fiber ingestion. Daily physical activity and energy expenditure were enhanced. The coaching program was able to induce immediate health benefits using a strategy with the patient at the core of promoting his own lifestyle changes. In conclusion, the nutritional coaching strategy detailed was effective at helping our patient develop new eating patterns and improve related health parameters.

Single Nucleotide Polymorphisms in Carnosinase Genes (CNDP1 and CNDP2) are Associated With Power Athletic Status.

Carnosine (ß-alanyl-L-histidine), abundantly found in skeletal muscle, plays an important role during exercise, especially for high-intensity contractions. Variability in muscle carnosine content between individuals exists and may also be explained by different genetic bases, although no study has addressed the association of polymorphisms in genes related to carnosine metabolism in athletes. This study aimed to investigate the frequency of single nucleotide polymorphisms (SNPs) in the carnosinase genes (CNDP1 and CNDP2) in a large Brazilian cohort of athletes and nonathletes. Eight SNPs were compared between a representative cohort of elite athletes from Brazil (n = 908) and a paired group of nonathletes (n = 967). The athletes were stratified into three groups: endurance (n = 328), power (n = 415), and combat (n = 165). The CNDP2 rs6566810 (A/A genotype) is overrepresented in endurance athletes, but only in international-level endurance athletes. Three SNPs (CNDP2 rs3764509, CNDP2-CNDP1 rs2346061, and CNDP1 rs2887) were overrepresented in power athletes compared with nonathletes. Carriers of the minor allele had an increased odds ratio of being a power athlete. For the rs2346061, no significant difference was observed in genotype frequencies between power and combat sports athletes, but for rs2887 the power and combat groups showed an inverse genotype distribution. In conclusion, we found that minor alleles carriers for CNDP2 rs3764509 (G-allele), CNDP2-CNDP1 rs2346061 (C-allele), and CNDP1 rs2887 (A-allele) are more likely to be a power athlete. These polymorphisms may be novel genetic markers for power athletes. Furthermore, these results are suggestive of a distinct CNDP genotype for sporting development.

Dietary protein supplementation in the elderly for limiting muscle mass loss.

Supplementation with whey and other dietary protein, mainly associated with exercise training, has been proposed to be beneficial for the elderly to gain and maintain lean body mass and improve health parameters. The main objective of this review is to examine the evidence provided by the scientific literature indicating benefit from such supplementation and to define the likely best strategy of protein uptake for optimal objectified results in the elderly. Overall, it appears that an intake of approximately 0.4 g protein/kg BW per meal thus representing 1.2-1.6 g protein/kg BW/day may be recommended taking into account potential anabolic resistance. The losses of the skeletal muscle mass contribute to lower the capacity to perform activities in daily living, emphasizing that an optimal protein consumption may represent an important parameter to preserve independence and contribute to health status. However, it is worth noting that the maximal intake of protein with no adverse effect is not known, and that high levels of protein intake is associated with increased transfer of protein to the colon with potential deleterious effects. Thus, it is important to examine in each individual case the benefit that can be expected from supplementation with whey protein, taking into account the usual protein dietary intake.

Dual effects of a high-protein diet on DSS-treated mice during colitis resolution phase.

The impact of the dietary protein level on the process of colonic mucosal inflammation and subsequent recovery remains largely unknown. In this study, we fed DSS-treated mice with either a normoproteic (NP) or a high-protein (HP) isocaloric diet from the beginning of the 5-day dextran sulfate sodium (DSS) treatment to 14 days later. Measurements of colitis indicators (colon weight:length ratio, myeloperoxidase activity, cytokine expressions) showed a similar level of colonic inflammation in both DSS groups during the colitis induction phase. However, during the colitis resolution phase, inflammation intensity was higher in the DSS-HP group than in the DSS-NP group as evidenced by higher inflammatory score and body weight loss. This coincided with a higher mortality rate. In surviving animals, an increase in colonic crypt height associated with a higher number of colon epithelial cells per crypt, and TGF-ß3 content was observed in the DSS-HP vs. DSS-NP group. Moreover, colonic expression patterns of tight junction proteins and E-cadherin were also different according to the diet. Altogether, our results indicate that the HP diet, when given during both the induction and resolution periods of DSS-induced colitis, showed deleterious effects during the post-induction phase. However, HP diet ingestion was also associated with morphological and biochemical differences compatible with higher colonic epithelium restoration in surviving animals, indicating an effect of the dietary protein level on colonic crypt repair after acute inflammation. These data highlight the potential impact of the dietary protein amount during the colitis course.

Loss of strength capacity is associated with mortality, but resistance exercise training promotes only modest effects during cachexia progression.

AIMS: Resistance exercise training (RET) has been adopted as non-pharmacological anti-catabolic strategy. However, the role of RET to counteract cancer cachexia is still speculative. This study aimed to verify whether short-term RET would counteract skeletal muscle wasting in a severe cancer cachexia rat model. MAIN METHODS: Wistar rats were randomly allocated into four experimental groups; 1) untrained control rats (control), 2) rats submitted to RET (control+RET), 3) untrained rats injected with Walker 256 tumor cells in the bone marrow (tumor) and 4) rats injected with Walker 256 tumor cells in the bone marrow and submitted to RET (tumor+RET). KEY FINDINGS: Tumor group displayed skeletal muscle atrophy fifteen days post tumor cells injection as assessed by plantaris (-20.5%) and EDL (-20.0%) muscle mass. EDL atrophy was confirmed showing 43.8% decline in the fiber cross sectional area. Even though RET increased the lactate dehydrogenase protein content and fully restored phosphorylated form of 4EBP-1 to the control levels in skeletal muscle, it failed to rescue muscle morphology in tumor-bearing rats. Indeed, RET did not mitigated loss of muscle function, anorexia, tumor growth or mortality rate. However, loss of strength capacity (assessed by 1-RM test performance) demonstrated a negative correlation with rats' survival (p=0.02; r=0.40), suggesting that loss of strength capacity might predict cancer mortality. SIGNIFICANCE: These results demonstrated that bone marrow injection of Walker 256 tumor cells in rats induces cancer cachexia, strength capacity is associated with cancer survival and short-term RET promotes only modest effects during cachexia progression.